This disclosure is directed to methods and systems for perfusing, in a defined and controlled manner, one or more organs, tissues or the like (hereinafter “organs”) to sustain, maintain or improve the viability of the organs.
Perfusion apparatus for transplantable organs are described in the scientific and patent literature. For example, U.S. Pat. No. 6,977,140, assigned to Organ Recovery Systems, Inc., which is hereby incorporated by reference herein in its entirety, describes such an apparatus. U.S. Pat. No. 6,977,140 does not, however, address certain aspects of perfusing a multi-inflow organ, such as a human liver.
Ideally organs are harvested in a manner that limits their warm ischemia time. Unfortunately, many organs, especially from non-beating heart donors, are harvested after extended warm ischemia time periods, e.g., 45 minutes or more. Machine perfusion of these organs at low temperature is preferable (Transpl Int 1996 Daemen). Further, low temperature machine perfusion of organs at low pressures is also preferable (Transpl. Int 1996 Yland). Roller or diaphragm pumps are often used to deliver perfusate at controlled pressures. Numerous control circuits and pumping configurations are used to achieve preferable perfusion conditions. See, for example, U.S. Pat. Nos. 5,338,662 and 5,494,822 to Sadri; U.S. Pat. No. 4,745,759 to Bauer et al.; U.S. Pat. Nos. 5,217,860 and 5,472,876 to Fahy et al.; U.S. Pat. No. 5,051,352 to Martindale et al.; U.S. Pat. No. 3,995,444 to Clark et al.; U.S. Pat. No. 4,629,686 to Gruenberg; U.S. Pat. Nos. 3,738,914 and 3,892,628 to Thorne et al.; U.S. Pat. Nos. 5,285,657 and 5,476,763 to Bacchi et al.; U.S. Pat. No. 5,157,930 to McGhee et al.; and U.S. Pat. No. 5,141,847 to Sugimachi et al.
Use of the above described pumps for machine perfusion of organs, however, may introduce a risk of under- or over-pressurization of the organ. High pressure perfusion, above about 60 mm Hg, for example, can wash off the vascular endothelial lining of the organ and damage organ tissue. In particular, at hypothermic temperatures, an organ does not have neurological or endocrinal connections to protect itself by dilating its vasculature under high pressure. Low pressure perfusion may provide insufficient perfusate to the organ resulting in organ failure.
This concern over precise control is particularly acute in multi-inflow organs. In the living liver, blood flows into the organ via the portal vein and the hepatic artery. The blood combines in the sinusoids of the liver, and then flows out through the hepatic vein. In vivo, the hepatic artery receives relatively higher pressure arterial blood (ca. 100 mmHg), while the portal vein receives relatively lower pressure venial blood (ca. 18 mmHg). A system of vascular tension and sphincters regulates the relative resistance of blood through the portal vein and hepatic artery to manage proper flow from each inflow port into the sinusoids despite the unequal initial pressures.
During organ perfusion preservation, a goal is to perfuse fluids through the vessels of the ex vivo liver (1) in sufficient volume, i.e., flow, to enable proper dilution of waste products and proper provision of nutrients; and (2) at sufficient pressure to maintain vessel patency while limiting maximum flow and pressure to avoid damage. In a single inflow organ like the kidney, for example, this often is achieved simply by regulating the pressure and flow into the single inflow artery within well-defined minimum and maximum pressure and flow therapeutic windows. Regulation methods for single inflow organs are well known.
Conventionally, flow regulation into a liver is treated just as in a kidney. The portal vein pressure and the hepatic artery pressure, and respectives flows, are separately and independently maintained within well-defined therapeutic windows between maximum and minimum levels, regulated to a constant level of pressure or flow, or a combination of both. Methods of separate and independent regulation of portal and hepatic pressure and flow are well known.